👤 P H Rheinstein

Smokers are 30 to 40 percent more likely to develop type 2 diabetes than non-smokers. A type 2 diabetes gene, Tcf7L2, which had lost activity, caused rats to consume more nicotine. In the present study, we used data from the UK Biobank to examine the relationship of smoking, type 2 diabetes, and Tcf7L2 in human subjects. The Genotype TT, linked to type 2 diabetes, smoked the least. But because of the large sample size (approximately 111,000 subjects) the tiny difference in cigarettes smoked daily by each genotype group (effect size), while statistically significant, is probably clinically meaningless. The average subject smoked 19 cigarettes daily, with a difference of 0.12 cigarette between each genotype group. The fact that Tcf7L2 is involved in nicotine addiction in rats but not in humans, as UKBB data suggest, is hardly surprising. Humans and rodents descended from a common ancestor about 80 million years ago, with rats and mice diverging between 12 and 24 million years ago. Thus, over millions of years Show less

Glioma susceptibility is inversely related to a history of allergies and atopy. Lung allergies are associated with 30% lower glioma susceptibility, compared to no lung allergies. Asthma and eczema also reduce the chance of glioma. However, the effect of allergy on glioma survival is not well characterized. Because of the allergy-glioma inverse relationship we examined the association of allergy with glioma survival in The Cancer Genome Atlas (TCGA). We evaluated the association between allergy and overall survival in TCGA Glioma (LGG) dataset. In order to have a sample of sufficient size to analyze, we classified as allergic any patient who answered yes to any of the manifestations of allergy that were queried. We analyzed data from 526 patients with glioma. History of allergy conferred a survival advantage on glioma patients, when stratified by tumor histologic grade (p = 0.049). Because allergy confers a favorable prognosis, we performed Cox regression. The effect of allergy on survival was significant (p = 0.025, HR 0.525, 95% CI 0.299-0.924), independent of the effect of chromosome 1p (p < 0.001, HR 93.4, 95% CI 16-546) and 19q (p = 0.801, HR 1.2, 95% CI 0.23-6.9) codeletion or TP53 mutation (p = 0.015, HR 2.7, 95% CI 1.2-5.9), unrelated to TERT expression (p = 0.365, HR 1.1, 95% CI 0.89-1.4) or ATRX mutation (p = 0.904, HR 1.04, 95% CI 0.51-2.14), independent of tumor grade (grade 2 versus grade 3, p = 0.004, HR 2.2, 95% CI 1.3-3.8), not independent of histology (oligodendroglioma and oligoastrocytoma, NOS versus astrocytoma, p = 0.08, HR 0.62, 95% CI 0.36-1.1). Diminished RNA expression of three loci, having reproducible genetic associations with allergic disease risk, are significantly associated with increased survival in glioma: FOSL2, APOBR, and NCF4. Diminished NCF4 copy number is significantly associated with reduced survival (D). Our finding of the improved prognosis that allergy confers on glioma increases the potential importance of understanding the allergy-glioma inverse association. If the mechanism could be more clearly elucidated, new, more effective treatments and preventive measures may be developed. Further studies are warranted. Show less